Faculty Bibliography

In this investigation, the effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospectively assessed. This investigation was a secondary analysis of a randomized, double-blind, placebo-controlled, parallel-group study in which adult patients received adjunctive lamotrigine (n=32) or placebo (n=38) for a 7-week dose escalation phase, followed by a 12-week maintenance phase, for primary generalized tonic-clonic (PGTC) seizures. Mood symptoms were assessed with the Beck Depression Inventory, second edition (BDI-II), the Profile of Mood States (POMS), and the Cornell Dysthymia Rating Scale-Self-Report (CDRS). Mean (SD) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups (lamotrigine 18.3 (12.1), placebo 16.8 (12.0)). At the end of the maintenance phase, mean (SD) improvement from baseline was greater with lamotrigine than placebo with respect to BDI-II score (lamotrigine 8.9 (7.6), placebo 1.7 (8.5), P=0.01) and POMS total score (lamotrigine 32.0 (30.4), placebo 6.5 (32.3), P=0.03) and numerically greater with lamotrigine than placebo for CDRS score (lamotrigine 7.3 (7.8), placebo 4.1 (13.9), P=0.50). Among the subset of patients with at least mild depression (BDI-II score10), mean improvement from baseline was numerically, but not statistically significantly, greater with lamotrigine (11.5, n=13) than placebo (3.1, n=18) (P=0.054). Median percentage reductions in seizure frequency were significantly greater with lamotrigine than placebo during the escalation phase, the maintenance phase, and the escalation and maintenance phases combined for PGTC seizures and all generalized seizures. However, improvement in seizure frequency was not correlated with improvement in mood (r=0.1, P=ns). Compared with placebo, lamotrigine improved mood symptoms independently of seizure reduction in patients with generalized seizures. Lamotrigine may be useful in treating patients with epilepsy and comorbid depressive symptoms.

Antiepileptic drugs (AEDs) are commonly utilized for nonepileptic conditions, including various psychiatric disorders and pain syndromes. Evidence for their benefit in these nonepileptic conditions varies widely among different drugs, but there is, in general, a paucity of published multicenter randomized double-blind trials. Variable levels of evidence suggest that lamotrigine and the vagal nerve stimulator have antidepressant properties. Carbamazepine, valproate, lamotrigine, and oxcarbazepine appear to have mood stabilizing properties while gabapentin, pregabalin, and tiagabine have anxiolytic benefits. Barbiturates, topiramate, and possibly phenytoin may precipitate or exacerbate depression. Underlying depression and anxiety symptoms may be exacerbated by levetiracetam, while psychotic symptoms have rarely been reported with topiramate, levetiracetam, and zonisamide. Pregabalin, gabapentin, carbamazepine, and oxcarbazepine have been used to treat neuropathic pain such as postherpetic neuralgia, and diabetic polyneuropathy. Topiramate and divalproex sodium have utility in the prophylaxis or acute treatment of migraine. Further rigorous studies are needed to clarify the utility of AEDs in nonepileptic conditions

BACKGROUND:Mood disorder symptoms are common in patients with epilepsy. Since antiepileptic drugs (AEDs) can affect these symptoms, knowledge of the psychotropic properties of AEDs is crucial. We review most studies of the psychotropic effects of AEDs that have involved potential psychiatric applications and have been reported in the psychiatric literature. METHODS:We conducted a comprehensive literature search to identify relevant clinical trial reports on the efficacy of AEDs for mood disorders. RESULTS:There have been few randomized controlled trials studying AED psychotropic properties in patients with epilepsy, but some randomized controlled trials of potential psychiatric indications for AEDs have been published. Data from these studies suggest that specific AEDs have mood stabilizing, anxiolytic, and antidepressant properties, while others may elicit depression, agitation, or psychosis. CONCLUSION/CONCLUSIONS:Antiepileptic drug selection should consider potential effects on mood and behavior.

Sexual dysfunction is common among patients with epilepsy, but many clinicians do not include inquiries about this aspect of the patient's health in their routine evaluations. This article presents approaches for taking a sexual history and for discussing sexual problems. The utility of standardized sexual dysfunction questionnaires is reviewed and the important elements of appropriate and effective counseling are highlighted.